The main objective of this research is to aid in the design of new antitumor agents and therapeutic regimens based on: 1) the properties of the enzymes dihydrofolate reductase and thymidylate synthase, their kinetics and interaction with ligands, 2) the role of unnatural diastereomers at C-6 of tetrahydrofolate derivatives in therapy, and 3) evaluation of folate analogs as enzyme inhibitors and inhibitors of microbial growth.